ABSTRACT ? Administrative Core Fusion-positive alveolar rhabdomyosarcoma (ARMS) remains one of the most fatal but least understood cancers of childhood. Despite the 1993 identification of the PAX3-FOXO1 fusion protein as a key oncogenic driver of ARMS, treatment strategies for affected children remain unchanged. Thus the overarching goal of this FusOnC2 Center is to advance the therapeutic tractability of the PAX3-FOXO1 fusion protein in ARMS by comprehensively identifying the druggable co-regulators, modulators, and intrinsic activities of PAX3-FOXO1. In support of this, the Administrative Core will provide leadership, oversight, coordination, integration, dissemination and evaluation for the Center and connect it to the NCI FusOnC2 Consortium. Given our multi-disciplinary, multi-institutional team, these activities will enhance scientific rigor and accelerate our collective progress. Overall PIs Corinne Linardic, MD, PhD, and Christopher Counter, PhD will lead this Core, supported by the Executive Committee, Scientific Advisory Board (SAB), and administrative staff, including an experienced Center Administrator and an expert Financial Manager. Drs. Linardic and Counter, and the Executive Committee also will work closely with the NCI Program Officer, Project Scientist, and FusOnC2 Consortium Steering Committee regarding Center plans and direction. The Administrative Core proposes the following Specific Aims: 1) Provide organizational and logistical support for component activities; 2) Coordinate and enhance interactions among Center components; 3) Provide financial management and ensure fiscal and regulatory compliance; 4) Monitor scientific progress and scientific rigor; 5) Disseminate discoveries and collaborate; and 6) Establish mechanisms for internal and external review. Through the Center Executive Committee?s regular meetings, the Core will manage, coordinate, and integrate scientific activities across the Projects and Cores, provide transparency in decision-making, and facilitate participation in FusOnC2 Consortium activities. In addition to the Executive Committee meetings, the Administrative Core will coordinate meetings of a ?Quantitative Sciences Working Group? to provide a layer of cross-Project data review and transparency, and to identify and ameliorate risks, including analyses that need to be confirmed or replicated by others, thus helping to ensure reproducibility. In conjunction with the FusOnC2 Consortium Steering Committee, the Administrative Core will develop and implement policies for timely data sharing and publication. The Administrative Core will serve as the ?hub? for our Center?s activities to accelerate progress and enhance rigor, and as the link to other FusOnC2 Centers for development and conduct of collaborative Consortium projects. Through our outreach plan, the Core will nurture trainees? career development and promote data and resource sharing. This Center is committed to full participation in FusOnC2 Consortium activities, and the research team welcomes this opportunity to apply ambitious new technologies and approaches to solve the problem of fusion protein-fueled cancers.